The broad objective of the proposed research is to reach a better understanding of the mechanisms underlying neurotrophic control of skeletal muscles. We will study soluble nerve proteins (SNP) which, as determined in preliminary experiments, appear to exert "trophic" effects on embryonic muscles. Central to our research strategy is to combine several approaches involving effects of SNP on transmission-related molecules in muscles during development, adulthood and aging. We plan to: (a) extract and further fractionate neurogenic proteins conveyed by axonal transport: (b) determine whether they are released by nerves "in vitro;" (c) assess their effects on growth, development, acetylcholine receptors (AChR), and molecular forms of acetylcholinesterase (AChE), of embryonic muscle cells in culture; and, (d) explore whether they delay or reverse degeneration of denervated muscle "in vitro" as relates to changes in AChR and the neuromuscular junction specific 16S-AChE. The significance attached to identification and definition of neurotrophic substances goes beyond attaining an increased knowledge on the mechanisms involved in nerve-muscle interactions. In fact, results from studies such as the one proposed may provide information on the role of trophic substances in normal development, congenital abnormalities, senility, and toxic effects of the environment on the nervous system.